The Rational Use of Antibiotics

1
The Rational Use of Antibiotics

• Victor Lim
• International Medical University
• Kuala Lumpur, Malaysia

2
Antibiotics

• One of the most commonly used group of drugs
• In USA 23 million kg used annually 50 for
  medical reasons
• May account for up to 50 of a hospitals drug
  expenditure
• Studies worldwide has shown a high incidence of
  inappropriate use

3
Reasons for appropriate use

• Avoid adverse effects on the patient
• Avoid emergence of antibiotic resistance -
  ecological or societal aspect of antibiotics
• Avoid unnecessary increases in the cost of health
  care

4
Ecological/Societal Aspect

• Antibiotics differ from other classes of drugs
• The way in which a physician and other
  professionals use an antibiotic can affect the
  response of future patients
• Responsibility to society
• Antibiotic resistance can spread from
• bacteria to bacteria
• patient to patient
• animals to patients

5
Prescribing an antibiotic

• Is an antibiotic necessary ?
• What is the most appropriate antibiotic ?
• What dose, frequency, route and duration ?
• Is the treatment effective ?

6
Is an antibiotic necessary ?

• Useful only for the treatment of bacterial
  infections
• Not all fevers are due to infection
• Not all infections are due to bacteria
• There is no evidence that antibiotics will
  prevent secondary bacterial infection in patients
  with viral infection

7
Arroll and Kenealy, Antibiotics for the common
cold. Cochrane Database of Systematic Reviews.
Issue 4, 2003

• Meta-analysis of 9 randomised placebo controlled
  trials involving 2249 patients
• Conclusions There is not enough evidence of
  important benefits from the treatment of upper
  respiratory tract infections with antibiotics and
  there is a significant increase in adverse
  effects associated with antibiotic use.

8
Is an antibiotic necessary ?

• Not all bacterial infections require antibiotics
• Consider other options
• antiseptics
• surgery

9
Choice of an antibiotic

• Aetiological agent
• Patient factors
• Antibiotic factors

10
The aetiological agent

• Clinical diagnosis
• clinical acumen
• the most likely site/source of infection
• the most likely pathogens
• empirical therapy
• universal data
• local data

11
Importance of local antibiotic resistance data

• Resistance patterns vary
• From country to country
• From hospital to hospital in the same country
• From unit to unit in the same hospital
• Regional/Country data useful only for looking at
  trends NOT guide empirical therapy

12
The aetiological agent

• Laboratory diagnosis
• interpretation of the report
• what is isolated is not necessarily the pathogen
• was the specimen properly collected ?
• is it a contaminant or coloniser ?
• sensitivity reports are at best a guide

13
Patient factors

• Age
• Physiological functions
• Genetic factors
• Pregnancy
• Site and severity of infection
• Allergy

14
Antibiotic factors

• Pharmacokinetic/pharmacodynamic (PK/PD) profile
• absorption
• excretion
• tissue levels
• peak levels, AUC, Time above MIC
• Toxicity and other adverse effects
• Drug-drug interactions
• Cost

15
PK/PD Parameters

• Increasing knowledge on the association between
  PK/PD parameters on clinical efficacy and
  preventing emergence of resistance
• Enabled doctors to optimise dosage regimens
• Led to redefinition of interpretative breakpoints
  in sensitivity testing

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Important PK/PD Parameters
Important PK/PD Parameters
Time above MIC Proportion of the dosing
interval when the drug concentration exceeds the
MIC
8
6
Drug A
Drug A
Drug B
4
Drug B
Antibiotic concentration (ug/ml)
2
B
B
0
Time
A
Time above MIC
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Important PK/PD Parameters
Area under the curve over MIC
AUC/MIC is the ratio of the AUC to MIC Peak/MIC
is the ratio of the peak concentration to MIC
PEAK
Antibiotic concentration
MIC
Time
18
PK/PD and Antimicrobial Efficacy

• 2 main patterns of bacterial killing
• Concentration dependent
• Aminoglycosides, quinolones, macrolides,
  azalides, clindamycin, tetracyclines,
  glycopeptides, oxazolidinones
• Correlated with AUC/MIC , Peak/MIC
• Time dependent with no persistent effect
• Betalactams
• Correlated with Time above MIC (TgtMIC)

Craig, 4th ISAAR, Seoul 2003
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Goal of therapy based on PK/PD
Pattern of Activity Antimicrobials Goal of therapy and relevant PK/PD Parameter
Concentration dependent killing AMGs, Quinolones, Daptomycin, ketolides, Macrolides, azithro-mycin, clindamycin, streptogramines,tetracyclines, glycopeptides, oxazolidinones Maximise concentrations AUC/MIC, peak/MIC Use high doses daily dosing for some agents
Time dependent killing with no persistent effects Betalactams Maximise duration of exposure TgtMIC Use more frequent dosing longer infusion times including continuous infusion
20
Cost of antibiotic

• Not just the unit cost of the antibiotic
• Materials for administration of drug
• Labour costs
• Expected duration of stay in hospital
• Cost of monitoring levels
• Expected compliance

21
Choice of regimen

• Oral vs parenteral
• Traditional view
• serious parenteral
• previous lack of broad spectrum oral antibiotics
  with reliable bioavailability
• Improved oral agents
• higher and more persistent serum and tissue
  levels
• for certain infections as good as parenteral

22
Advantages of oral treatment

• Eliminates risks of complications associated with
  intravascular lines
• Shorter duration of hospital stay
• Savings in nursing time
• Savings in overall costs

23
Duration of treatment

• In most instances the optimum duration is unknown
• Duration varies from a single dose to many months
  depending on the infection
• Shorter durations, higher doses
• For certain infections a minimum duration is
  recommended

24
Recommended minimum durations of treatment
25
Monitoring efficacy

• Early review of response
• Routine early review
• Increasing or decreasing the level of treatment
  depending on response
• change route
• change dose
• change spectrum of antibacterial activity
• stopping antibiotic

26
Antimicrobial Resistance Key Prevention
Strategies
Susceptible Pathogen
Pathogen
27
12 Steps to Prevent Antimicrobial Resistance
28
Conclusions

• Antibiotic resistance is a major problem
  world-wide
• Resistance is inevitable with use
• No new class of antibiotic introduced over the
  last two decades
• Appropriate use is the only way of prolonging the
  useful life of an antibiotic